Date of Award
Master of Science (MS)
Samuel B. Kombian
Capsaicin is a naturally occurring alkaloid derived from chili pepper fruits. Capsaicin is a unique compound due to its ability to trigger a desensitization after the initial neuronal excitation in the nerve terminal expressing TRPVI as well as generation of long-Iasting nerve defunctionalization at sufficient dosing. Capsaicin has a beneficial role in the treatment of pain, cancer, obesity, diabetes, gastrointestinal, cardiovascular, dermatological conditions, and several other pathologies. In this study, we investigated the effect of capsaicin on the function of a cloned α7 subunit of human nicotinic acetylcholine receptor (α7-nAChR) expressed in Xenopus laevis oocytes using the two electrode voltage clamp method. Capsaicin showed maximum potency of inhibition of ACh-induced currents with an IC50 value of 8.6 μM (with 50% inhibition). The mechanisms of capsaicin's action on the α7-nAChR were further investigated and found to be independent of membrane potential. Furthermore, capsaicin (10 μM) did not affect the activity of Ca2+ dependent CI- channels since the extent of inhibition by capsaicin was unaltered by the intracellularly injected Ca2+ chelator BAPTA and perfusion with Ca2+ free bathing solution containing 2 mM Ba2+. The effect of capsaicin was associated with decreased ACh efficacy, and the inhibition was not reversed by increasing ACh concentrations, suggesting a non-competitive inhibition of nicotinic receptors. Capsaicin not only had an inhibitory effect on α7-nAChRs but also on the other members of cys-loop family of ligand-gated ion channels including: α3β2, α4β4, α4β2, α1β1, and α3β4 nACh receptors, 5HT3 receptor, and glycineα] and α3-receptor, while, it caused potentiation of glycine α2-receptor function. In conclusion, our results indicate that capsaicin inhibits the function of the α7-nACh receptor, and emphasizes the importance of a7-nACh receptor for future pharmacological toxicological profiling.
Alzaabi, Asma Hassan Ali Muftah, "The effects of Capsaicin on the function of human α7 Nicotine Acetylcholine receptors expressed in Xenopus Oocytes." (2018). Medical Education Theses. 1.